TRICYCLIC ANTIDEPRESSANTS (TCA), AND SNRIs (SEROTONIN NOREPINEPERHINE RE-UPTAKE INHIBITORS), AND OTHER ANTIDEPRESSANTS FOR THE TREATMENT OF DYSPEPTIC SYMPTOMS

In an effort to find therapeutic measures to block more noxious dyspeptic or gastroparetic symptoms such as gut (visceral) pain, nausea and feelings of fullness, researchers have again borrowed from the psychiatric drug armamentarium.

As we previously mentioned, many of the drugs used for treating nausea come from a very old class of drugs called the phenothiazines. The more commonly applied ones for nausea and vomiting are: Thorazine®, Compazine® and Phenergan®. These drugs were developed for commercial use in the 1940s and originally designed to treat major psychoses like schizophrenia but gained wide use in many other applications. This tells us that these old drugs act upon many numerous and different receptors throughout the body, leading to a long list of side effects.

The chemical birthplace for the tricyclic antidepressants (TCA) comes from the phenothiazine drugs. Tricyclic drugs get their name from their chemical structure, having a three-ringed molecular carbon core.

TCAs have seen a revival of use in the application of so-called “functional bowel disorders”. Some examples of functional bowel disorders are irritable bowel syndrome, functional dyspepsia, and functional abdominal pain. These subjective diagnostic labels are wholeheartedly endorsed by the researchers who devised them at meetings held in Rome, called the Rome Criteria for functional GI disorders. Research into functional bowel disorders has had a historical bias for drawing connections to underlying psychiatric issues to explain bowel symptoms.

That said, there are biological explanations for the brain-gut approach to treat gut symptoms. Remember, there are numerous serotonin receptors (seven sub-classes of these receptors have been discovered to date) found throughout the brain and gut. As well, dopamine receptors and receptors to the chemical nerve transmitter—called norepinephrine—are ubiquitous between the nervous wiring within the brain, autonomic nervous system and enteric nerves. The chemicals our body naturally produces to bind to the various receptors mentioned are called neurotransmitters and are responsible for control of normal brain functions such as mood, pain, sleep and thinking.

TCAs have a very mixed response on a wide variety of neurotransmitters and receptors throughout the gut-brain connection. Consequently, they have numerous side effects such as dry mouth, blurred vision, sleepiness, difficulty urinating, erectile dysfunction, changes in blood pressure, cardiac toxicity, constipation, and delayed gastric emptying.

The side effects are dose-related, and often the TCAs used primarily for the management of digestive symptoms from functional gut disorders and motility problems are used at very low dosages.

While the standard belief in the general medical community is that TCAs work primarily through their action upon the central nervous system, this is ignoring a more plausible explanation.

The autonomic nervous system provides for transmission of noxious stimuli from the gut to the brain. In functional gut disorders, as well as in slow-transit motility diseases, published evidence shows an overall imbalance within the autonomic nervous system—usually with an overabundance of outflow from the sympathetic nervous system. While the mapping out of noxious stimuli, such as visceral pain, has been extensively studied, little work has been done to map out the signal transmission of nausea/vomiting generated by gastroparesis.

TCAs do work for many to help control visceral pain and nausea. The way in which they work may be through their action to block sympathetic outflow from the gut, thus diminishing the awareness within the brain. The impact upon sympathetic signalling seems to be of greater importance because the TCAs also tend to suppress overall function of the parasympathetic nervous system leading to a medication-induced delay in gastric emptying.

The most commonly used TCA, and the one with the most published evidence for use in GI functional and motility problems, is amitriptyline (Elavil®, Endep®, Emitrip®, Enovil®). Amitriptyline, however, has the greatest impact on slowing down gut transit as a side effect. In GI motility problems, like gastroparesis, where gut transit is already slowed, a better TCA choice may be desipramine (Norpramin®, Pertofrane®), or

nortiptyline (Pamelor®, Aventyl®).

The SNRIs and other antidepressant medications

Newer-generation antidepressant medications have also been used to treat upper digestive symptoms, again with the theory of modulating major brain neurotransmitters to blunt the experience of distressing symptoms. Some of these agents such as remeron (Mirtazapine®) have a side effect of weight gain, something of value to counter unintentional weigh loss from gastroparesis.

Many people, too, have found gut-symptom relief from SNRI drugs such as Cymbalta® and Effexor XR®

The SSRI (selective serotonin re-uptake inhibitors) group of antidepressants is generally avoided for use in functional and motility gut disorders, primarily due to their high incidence of side effects of nausea, dizziness and dry mouth as well as sexual dysfunction.

As a family of drugs, antidepressants can be very helpful in controlling GI symptoms but they represent an enormously diverse group of medicines. To find the best therapy from this class of medical therapies, it would be recommended to seek the assistance of a psychiatrist. They are very knowledgeable regarding the various antidepressant medications, their safety profiles and side effects. Finding a psychiatrist, who understands and is supportive enough to work with you in optimizing digestive symptom management can be a great addition to your team of medical care providers.